Table 2.

Bone metabolism regulatory functions of FoxO transcription factors in osteoblast.

FoxOs	Effects on Bone	Functions in Osteoblast	Mechanisms	Cell/Mice Models	References
FoxO1, 3, and 4	bone mass (+); bone formation rate (BFR) (+)	osteoblast number (+); osteoblast apoptosis (-); oxidative stress (-)	osteoblast number (+) through osteoblastogenesis (+); osteoblast apoptosis (-) through a cell-autonomous mechanism that enhances oxidative stress	conditional deletion of FoxO1, 3, and 4 in 3-month-old mice	[26]
FoxO1	BFR (+); bone volume (+)	osteoblast numbers (+); oxidative stress (-)	ROS activates the p53 signaling cascade, inducing cell cycle arrest and limiting osteoblast proliferation.	FoxOs deletion mice in bone
FoxO3	vertebral bone mass (+); BFR (+)	osteoblast number (+), osteoblast apoptosis (-), oxidative stress (-)	ROS (-); phosphorylation of p66 Shc (-)	mice overexpressing FoxO3 under the control of the osteocalcin promoter
FoxO1	bone mass (+), BFR (+) bone volume (+)	osteoblast proliferation (+), oxidative stress (-)	FoxO1 interacts with ATF4 and promotes amino acid import to favor the protein synthesis, such as glutathione. FoxO1 reduces ROS, activating a p53 signaling cascade, then promoting cell cycle.	FoxO1 deletion in mice from collagen1a1 expressing cells	[41]